Project Summary (from Parent Application) Osteoarthritis (OA) is the leading cause of disability worldwide. The inability of non-invasive techniques to quantify disease progression has limited understanding of the pathogenesis of OA. While numerous magnetic resonance imaging (MRI) methods have been proposed for imaging OA, analysis is often limited to a single tissue or performed using subjective scoring systems. We propose advanced three-dimensional MRI methods as well as advanced analysis tools to quantitatively study the spatial and temporal progression of OA across different tissues in the knee joint. This work will lead to a new understanding of OA pathogenesis by revealing relationships between changes in multiple tissues of the entire joint over time. This project aims to develop 3D imaging tools based on MRI to sensitively track changes of OA in all joint tissues simultaneously. Our specific aims are to (1) develop a robust ultra-short echo time based quantitative DESS method to obtain high-resolution 3D maps of apparent diffusion coefficient (ADC), T2 and T2* in multiple joint tissues, (2) Improve the signal and resolution of whole-joint sodium MRI at 3T using a novel phased array coil, (3) Develop and validate novel 3D analysis tools that will allow us to quantify changes in knee joint tissues spatially and over time and (4) Validate the ability of our protocol and analysis tools to quantitatively detect changes over time in the knees of subjects with OA of the knee. The innovation of this work lies in the development of novel imaging and analysis techniques that simultaneously offer quantitative measures of tissue integrity in cartilage, meniscus, synovium, and bone marrow. This novel data acquisition will be paired with an innovative three- dimensional analysis approach that will allow quantitative assessment of multiple joint tissues at a single time point and over time. The significance of this work is that we will be able to sensitively and quantitatively track changes of OA over time with accurate registration of multiple joint tissues. This will lead to new insights into OA pathogenesis and progression, as we will be able to relate changes in adjacent joint tissues and across time in subjects with OA.